With transscleral iontophoresis technology (EGP-437) developed by EyeGate Pharma, charged particles are delivered to the cornea to target the inflammation, Dr. Nguyen said. It may be possible to deliver higher ocular drug concentrations with this system than with traditional topical application, resulting in a sustained therapeutic effect and reduced dosing frequency.
In an initial phase III, non-inferiority anterior uveitis trial, 193 subjects were randomized to 2 EGP-437 iontophoresis treatments with placebo eye drops or 2 placebo iontophoresis treatments with prednisolone acetate eye drops. A similar response rate was achieved when EGP-437 treatment was compared to the standard of care treatment with prednisolone.
Further, fewer subjects in the EGP group had an IOP increase than in the prednisolone group (15%, n = 14 versus 25%, n = 24) Dr. Nguyen said. There were 2.4 times the number of incidents of IOP increase in the control, state-of-care arm, 41 versus 17.
A confirmatory phase III trial is underway. The primary endpoint is the proportion of subjects with anterior chamber cell count of zero at day 14.
New approaches are being explored in local immunomodulatory therapy, Dr. Nguyen said. Complement-based therapy in patients with active noninfectious intermediate, posterior, or panuveitis, is being investigated in an ongoing phase II clinical trial of intravitreal delivery of the complement inhibitor LFG316 (Novartis), a monoclonal antibody directed toward human C5.
Trials are in progress for intravitreal delivery of sirolimus (Santen), a novel immunoregulatory agent. This mTOR inhibitor is being assessed for management of patients with noninfectious uveitis of the posterior segment. In a 6-month, phase III study, patients were randomized to receive 44 µg, 440 µg, or 880 µg doses of intravitreal sirolimus at days 1, 60, and 120. The primary efficacy outcome was the percentage of subjects with vitreous haze equaling zero at month 5.
“For the primary endpoint, patients in the 440-µg group demonstrated statistically significant improvement (p = 0.25) over the 44-µg and 880-µg groups,” Dr. Nguyen said.
Results for a key secondary endpoint, the proportion of subjects with vitreous hemorrhage equaling zero or 0.5+ at month 5, were even more significant (p = 0.008). In the 440-µg group, 52.6% of subjects met this target compared to 43.1% in the 880-µg group and 35% in the 44-µg group.
The highest median gain in best-corrected visual acuity from baseline was 10.5 letters among patients in the 440-µg arm who had a baseline measurement <20/100 and displayed the most potential to improve, Dr. Nguyen added.
Based on study findings, it appears that intravitreal sirolimus 440 µg controls inflammation in target tissues in the posterior segment by inhibiting mTOR and can reduce inflammation while preserving vision.
“The benefit:risk profile seems to favor its potential use for the long-term treatment of noninfectious posterior segment uveitis,” Dr. Nguyen said.
Dr. Nguyen and colleagues in the Sirolimus study Assessing double-masKed Uveitis tReatment Study Group (SAKURA) published their findings in Ophthalmology in November 2016.